Gerhold Lynnette M, Rosewell Katherine L, Wise Phyllis M
Department of Neurobiology, Physiology, and Behavior, Division of Biological Sciences, University of California, Davis, Davis, California 95616-8536, USA.
J Neurosci. 2005 Jan 5;25(1):62-7. doi: 10.1523/JNEUROSCI.3598-04.2005.
Input from the suprachiasmatic nucleus (SCN) to gonadotropin-releasing hormone (GnRH) neurons is critical to the occurrence of regular cyclic GnRH secretion. It is thought that an essential neuropeptide in the SCN that communicates this cyclic information to GnRH neurons is vasoactive intestinal polypeptide (VIP) and that it may act through cAMP. We tested the hypothesis that (1) aging involves a blunting of cAMP diurnal rhythmicity in the SCN; (2) administration of antisense oligonucleotides (anti-oligos) against VIP, which produces an aging-like pattern in VIP, would lead to an aging-like suppression of cAMP; and (3) this in turn would lead to inhibition of the steroid-induced activation of GnRH neurons. We measured cAMP concentrations in the SCN and rostral preoptic nucleus throughout the day in young and middle-aged rats that were ovariectomized (OVX) or OVX and treated with estradiol. Our results show that cAMP concentrations exhibit a diurnal rhythm in young rats, and that this rhythm is totally abolished by the time rats are middle age. Administration of antisense oligonucleotides against VIP or random oligos suppresses VIP concentrations and abolishes the cAMP rhythm, leading to significantly reduced activation of GnRH neurons. Together, these findings strongly suggest that the SCN conveys diurnal information to GnRH neurons by driving VIP-dependent cAMP rhythms. In addition, aging involves deterioration in this VIP-driven rhythmicity, which impacts the ability of steroids to induce GnRH neuronal activation.
从视交叉上核（SCN）到促性腺激素释放激素（GnRH）神经元的输入对于规律性周期性GnRH分泌的发生至关重要。人们认为，SCN中一种将这种周期性信息传递给GnRH神经元的重要神经肽是血管活性肠肽（VIP），并且它可能通过环磷酸腺苷（cAMP）发挥作用。我们检验了以下假设：（1）衰老涉及SCN中cAMP昼夜节律的减弱；（2）给予针对VIP的反义寡核苷酸（反义寡聚物）会导致VIP出现类似衰老的模式，进而导致cAMP出现类似衰老的抑制；（3）这反过来会导致对类固醇诱导的GnRH神经元激活的抑制。我们在全天测量了切除卵巢（OVX）或切除卵巢并接受雌二醇治疗的年轻和中年大鼠的SCN和视前区头端的cAMP浓度。我们的结果表明，cAMP浓度在年轻大鼠中呈现昼夜节律，而在大鼠进入中年时这种节律完全消失。给予针对VIP的反义寡核苷酸或随机寡聚物会抑制VIP浓度并消除cAMP节律，导致GnRH神经元的激活显著减少。总之，这些发现强烈表明，SCN通过驱动依赖VIP的cAMP节律将昼夜信息传递给GnRH神经元。此外，衰老涉及这种由VIP驱动的节律性的恶化，这影响了类固醇诱导GnRH神经元激活的能力。
